NM_006747.4:c.211C>G

Variant names:

• chr11-65641132-C-G
• rs202042635
• NM_006747.4:c.211C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006747.4(SIPA1):​c.211C>G​(p.Arg71Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,246 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71C) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: SIPA1 NM_006747.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

Genes affected

SIPA1 (HGNC:10885): (signal-induced proliferation-associated 1) The product of this gene is a mitogen induced GTPase activating protein (GAP). It exhibits a specific GAP activity for Ras-related regulatory proteins Rap1 and Rap2, but not for Ran or other small GTPases. This protein may also hamper mitogen-induced cell cycle progression when abnormally or prematurely expressed. It is localized to the perinuclear region. Two alternatively spliced variants encoding the same isoform have been characterized to date. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1	NM_006747.4	c.211C>G	p.Arg71Gly	missense_variant	Exon 2 of 16	ENST00000534313.6	NP_006738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1	ENST00000534313.6	c.211C>G	p.Arg71Gly	missense_variant	Exon 2 of 16	1	NM_006747.4	ENSP00000436269.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152246 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152246 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74382

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.;T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.80	.;T;T;T
M_CAP	Pathogenic	0.65	D
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.8	L;.;.;L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.9	N;D;N;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0060	D;D;D;D
Sift4G	Benign	0.067	T;T;T;T
Polyphen		0.65	P;.;P;P
Vest4		0.19
MutPred		0.20		Loss of methylation at R71 (P = 0.0127);Loss of methylation at R71 (P = 0.0127);Loss of methylation at R71 (P = 0.0127);Loss of methylation at R71 (P = 0.0127);
MVP		0.87
MPC		1.8
ClinPred		0.88	D
GERP RS		4.5
Varity_R		0.15
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs202042635; hg19: chr11-65408603;